“For ATLAS, it was a different protocol. This was looking at giving the chemotherapy agent upfront,” says Sandip M. Prasad, MD, MPhil.
In this interview, Sandip M. Prasad, MD, MPhil, discusses the background behind the recent Journal of Urology paper, “Treatment of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer with UGN-102 ± Transurethral Resection of Bladder Tumor (TURBT) Compared to TURBT Monotherapy: A Randomized, Controlled, Phase 3 Trial (ATLAS).” Prasad is a urologist with Garden State Urology in Morristown, New Jersey.
Please describe the background for this study.
The disease space we were looking at for the ATLAS study was intermediate-risk, low-grade, non–muscle-invasive bladder cancer. That really involves an interesting group of patients; they come from different backgrounds. All these patients have low-grade bladder cancer, but they have 1 of 3 other types that are of interest and lead to higher rates of recurrence, more resections, more investigations. One of those is that patients can have large tumors, so greater than 3 cm. The second is that patients have multiple tumors, or what we call multifocal disease. So they have multiple tumors spread throughout the bladder, which is not uncommon. And the last is having recurrent bladder cancer, which again, is sort of a hallmark of this intermediate-risk space. These are patients that have had more than 1 recurrence in a year. And again, these recurrences are important, because the majority of these have to be managed with surgical resection. That's going to involve taking a patient to the operating room, putting them to sleep, holding their blood thinners potentially, putting instruments into the urethra, doing a resection. Given that the average age of these patients is 75, you're talking about a patient population that's generally older, has other comorbidities. And again, with the number 1 risk factor for bladder cancer being smoking, many of these patients also have existing cardiopulmonary disease, which again leads to the importance of trying to avoid surgical treatments in these patients if we can. Now, we've really never had treatments that primarily do that, other than going in and scraping a tumor away. That's called transurethral resection of bladder tumor, or TURBT. This is something that every single urologist does, and then we've used, historically, medications after a complete resection to try to limit or minimize the amount of cancer that comes back. These are treatments that again, all of us as urologists are very familiar with. These are things like BCG, intravesical immunotherapy, and there are some other potentially promising treatments coming down the road. For ATLAS, it was a different protocol. This was looking at giving the chemotherapy agent upfront. It's a really interesting agent. It's using a drug called mitomycin, which has been used historically in bladder cancer for many, many years, but always in the setting I alluded to previously, which is in the adjuvant setting, meaning we've resected a tumor completely, and therefore, we go in and put in the mitomycin, gemcitabine, or some other type of chemotherapy, afterwards to try to minimize either microscopic deposition or treating microscopic disease. The ATLAS study uses a proprietary product under investigation called UGN-102. This is mitomycin placed into something called a reverse thermal gel. It is a gel that is impregnated with mitomycin and allows for about 6 to 8 hours of continuous contact with the lining of the bladder surface. That's very different than when we put mitomycin in with saline or water, and the patient urinates it out within 1 or 2 hours. So again, the gel uses the same chemical we've used all along for bladder cancer treatment, but with a delivery device that allows for much longer exposure that we can achieve with just a fluid-based one that you can urinate out. This gel cannot be urinated out; it eventually dissolves away and is reabsorbed, but again, it takes 6 to 8 hours to do so. This is a phase 3 study, so there have been prior studies looking at this agent demonstrating safe safety and efficacy. But this is the first randomized controlled trial between UGN-102 and TURBT, so again, the standard of care using surgical resection as our control arm and then using intravesical instillation of this gel as the study arm. The drug is given the same way that many of our intravesical studies are designed, which is sort of after the model of BCG, which has kind of been our hallmark of intravesical instillation. The treatment is given once a week for 6 weeks. This can be done in the ambulatory setting in the office. It's done with a traditional catheter, so this doesn't really require any additional tools or instruments that the urologist may not have on hand other than the study drug itself. Treatments are given once a week for 6 weeks, and then patients were reexamined 6 weeks after the last treatment with a cystoscopy. And at that time, determination was made, either if they had a resection, to see if the tumor had come back in 3 months - and again, remember this is a population of patients that generally is at higher risk of recurrence - or patients who had received the gel alone, and to see if the tumor had come back as well. Importantly, these tumors were left in place at the original evaluation. So if patients had a biopsy at the very initial investigation, but not a resection of the tumor, a little pinch of the corner to make sure they had low-grade disease, and so both the TURBT arm and the instillation arm of UGN-102 both had existing tumors at the time of initial treatment. Then we looked back again at 3 months and tried to figure out if this was effective or not.
This transcript was edited for clarity.